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Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study
Open accessAbstract
Context: Growth hormone (GH) is prescribed for an increasing range of indications, but there has been concern that it might raise cancer risk. Published data are limited. Objective: To examine cancer risks in relation to GH treatment. Design: Cohort study. Setting: Population-based. Patients: Cohort of 23,984 patients treated with recombinant human GH (r-hGH) in eight European countries since this treatment was first used in 1984. Cancer expectations from country-specific national population statistics. Main Outcome Measures: Cancer incidence and cancer mortality. Results: Incidence and mortality risks in the cohort were raised for several cancer sites, largely consequent on second primary malignancies in patients given r-hGH after cancer treatment. There was no clear raised risk in patients with growth failure without other major disease. Only for bone and bladder cancers was incidence significantly raised in GH-treated patients without previous cancer. Cancer risk was unrelated to duration or cumulative dose of r-hGH treatment, but for patients treated after previous cancer, cancer mortality risk increased significantly with increasing daily r-hGH dose (P trend < 0.001). Hodgkin lymphoma (HL) incidence increased significantly with longer follow-up (P trend = 0.001 for patients overall and 0.002 for patients without previous cancer). Conclusions: Our results do not generally support a carcinogenic effect of r-hGH, but the unexplained trend in cancer mortality risk in relation to GH dose in patients with previous cancer, and the indication of possible effects on bone cancer, bladder cancer, and HL risks, need further investigation.
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“data from GH registries provide no evidence of an increase in risk of neoplasia with treatment.173,208,222-224”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [223]
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Wu, G., Dong, Y., Hu, Q., Ma, H., Xu, Q., Xu, K., Chen, H., Yang, Z., & He, M. (2023) · Cell Cycle · doi:10.1080/15384101.2023.2260163 · Cited by 11
“These findings suggest a potential association between recombinant hGH treatment and increased cancer incidence and mortality in patients with cancer history, as observed in a European cohort study [31].”
ResultJorge, A. A. L., Grimberg, A., Dattani, M., & Baron, J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-62520-3.00011-7 · Cited by 11
Giacomozzi, C. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.671361 · Cited by 11
Beck‐Peccoz, P., Höybye, C., Murray, R. D., Şimşek, S., Zabransky, M., Zouater, H., & Stalla, G. K. (2020) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018820943377 · Cited by 10
Velazquez, E. P., Miller, B. S., & Yuen, K. C. J. (2023) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2023.2290495 · Cited by 9
“Beyond postmarketing surveillance registries, a massive retrospective data collection study was performed in patients who received DGH therapy in the 1980s and 1990s, which resulted in the landmark SAGhE study [56–58].”
BackgroundJuriaans, A. F., Trueba-Timmermans, D. J., Kerkhof, G. F., Grootjen, L. N., Walet, S., Sas, T., Rotteveel, J., Zwaveling‐Soonawala, N., Stuart, A. A. V., & Hokken-Koelega, A. (2023) · Hormone Research in Paediatrics · doi:10.1159/000530420 · Cited by 8
Loche, S., Kanumakala, S., Backeljauw, P. F., Schwab, K. O., Lechuga-Sancho, A. M., Esmael, A., Urosevic, D., Boldea, A., & Zabransky, M. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s440009 · Cited by 8
“19 In KIGS, neoplasms of all-causality were reported in 0.7% of patients, and considered treatment related in 0.2% of patients (IR per 1000 PY not reported in publication).”
BackgroundInfluentialResearch on the Effects of Medications in Pregnancy and in Children
Horton, D. B., Hernández–Dı́az, S., Lasky, T., & Huybrechts, K. F. (2019) · Pharmacoepidemiology · doi:10.1002/9781119413431.ch22 · Cited by 8
Increased cancer risk in a cohort of patients with acromegaly in Israel
Duskin‐Bitan, H., Perez, A., Netzer, D., Cohen, A. D., Comaneshter, D. S., Beckenstein, T., Yaron, S., Zaina, A., Rudman, Y., Masri‐Iraqi, H., et al. (2025) · Endocrine Related Cancer · doi:10.1530/erc-24-0087 · Cited by 7
Increase of serum lipoprotein (a), an adverse effect of growth hormone treatment
Laron, Z. (2022) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2022.101503 · Cited by 7
Co-Occurrence of Acromegaly and Hematological Disorders: A Myth or Common Pathogenic Mechanism
Gupta, P., & Dutta, P. R. (2017) · Integrative Medicine International · doi:10.1159/000478932 · Cited by 7
Growth hormone rescue cerebellar degeneration in SCA3 transgenic mice.
Wu, S., Liu, K.-H., Cheng, W.-L., Su, S.-L., Lin, Y., Lin, T.-T., Cheng, Y.-S., Chang, J.-C., Wu, Y., & Liu, C. (2020) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2020.05.116 · Cited by 6
Backeljauw, P. F., Kanumakala, S., Loche, S., Schwab, K. O., Miller, B. S., Levy, R. A., McCormick, K. L., Zouater, H., Zabransky, M., & Campbell, K. (2022) · European Journal of Pediatrics · doi:10.1007/s00431-022-04409-8 · Cited by 7
“However, there is still uncertainty and thus requires further investigation [15].”
BackgroundHe, M., Deng, X., Wang, X., Wan, Y., Huang, J., Zhang, Z., & Niu, W. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2022.866295 · Cited by 7
“Of the 24 articles included, the outcome measure was all cause SMR in 7 articles (2, 13, 16–20), cancer SIR in 12 articles (1, 2, 5, 17, 19, 21–27), cancer SMR in 4 articles (16, 21, 25, 27), and second neoplasm in 8 articles (9, 10, 28–33).”
BackgroundInfluentialTidblad, A., Bottai, M., Smedby, K. E. E., Albertsson-Wikland, K. G., & Savendahl, L. S. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1360139 · Cited by 7
Pricci, F., Villa, M., Maccari, F., Agazio, E., Rotondi, D., Panei, P., & Roazzi, P. (2018) · Journal of Endocrinological Investigation · doi:10.1007/s40618-018-0980-3 · Cited by 7
Growth hormone replacement therapy in childhood-onset craniopharyngioma
van Iersel, L., van Schaik, J., & van Santen, H. M. (2025) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2025.101998 · Cited by 6
Growth hormone and radiation therapy: friend, foe, or both?
Bahamondes, V., & Wu, S. (2024) · Endocrine Related Cancer · doi:10.1530/erc-22-0371 · Cited by 6
Kamoun, C., Largent, E. A., & Grimberg, A. (2024) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001363 · Cited by 6
“Thus, the proposed reframing may not only face resistance from, but also counter a focusing illusion.”
BackgroundPalmieri, V. V., Lonero, A., Bocchini, S., Cassano, G., Convertino, A., Corica, D., Crinò, A., Fattorusso, V., Ferraris, S., Fintini, D., et al. (2019) · Growth Hormone & IGF Research · doi:10.1016/j.ghir.2019.08.003 · Cited by 6
Update on methods to enhance growth
Hodax, J. K., & DiVall, S. A. (2019) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000513 · Cited by 6
“Although a higher risk of malignancy specifically bone cancer was noted in GH-treated patients without isolated GHD or cancer history, the authors acknowledged that the underlying disorder associated with the GH treatment may account for the malignancy risk [8].”
BackgroundBackeljauw, P. F., Miller, B. S., Levy, R. A., McCormick, K. L., Zouater, H., Zabransky, M., & Campbell, K. (2021) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2020-0360 · Cited by 6
Ouyang, R., Gu, H., Yuan, J., Sun, Y., & Zhao, X. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1577396 · Cited by 5
Adverse events with usage of human growth hormone: a review
Branski, L. K., Thanedar, S., Deen, N., Cho, K. W., Liu, G., Hundeshagen, G., Herndon, D. N., & Sousse, L. E. (2025) · Discover Medicine · doi:10.1007/s44337-025-00474-8 · Cited by 5
“Increased cancer mortality and incidence were observed only in the high-risk group, primarily consisting of patients with prior malignancy and were significantly associated with higher daily rhGH doses risk [113].”
Gawrychowska, A., Iżycka‐Świeszewska, E., Lipska-Ziętkiewicz, B. S., Kuleszo, D., Bautembach-Minkowska, J., Łosin, M., & Stefanowicz, J. (2020) · Diagnostics · doi:10.3390/diagnostics10121067 · Cited by 6
“risk of bone and bladder cancer in the intermediate risk group including TS patients [17].”
BackgroundSomma, C. D., Scarano, E., Arianna, R., Romano, F., Lavorgna, M., Serpico, D., & Colao, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12020662 · Cited by 5
“While there was no statistically significant link found between GH replacement therapy and primary cancer recurrence, studies have found that GH therapy may enhance secondary neoplasia risk in CCS [14,15,23,79,81,82].”
BackgroundHealth behaviour of women with Turner Syndrome
Santi, M., Flück, C. E., Hauschild, M., Kuhlmann, B., Kuehni, C. E., & Sommer, G. (2021) · Acta Paediatrica · doi:10.1111/apa.15814 · Cited by 5
The Proteomic Signature of Recombinant Growth Hormone in Recreational Athletes
Esefeld, M., Pastor, A., de la Torre, R., Barroso, O., Aikin, R. A., Sarwath, H., Engelke, R., Schmidt, F., & Suhre, K. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab156 · Cited by 4
“Whether long-term use of hGH may be associated with other adverse events, especially a higher risk of developing primary or secondary cancers, remains controversial [13-15].”
BackgroundO’Neill, C., Gangat, M., & Radovick, S. (2022) · Endocrines · doi:10.3390/endocrines3040060 · Cited by 5
Safety of GH after treatment for childhood cancer
van Santen, H. M. (2020) · European Journal of Endocrinology · doi:10.1530/eje-20-0965 · Cited by 4
Hong, Y. H., Kim, D. G., Lee, J. H., Jung, M. J., & Choi, C. Y. (2020) · Journal of Clinical Research in Pediatric Endocrinology · doi:10.4274/jcrpe.galenos.2020.2019.0223 · Cited by 4
“Additionally, a recent large cross-European cohort study [14] also showed no clear, raised cancer risk in patients with growth failure without other major disease.”
Background
Metadata
- Authors
- Swerdlow, A. J., Cooke, R., Beckers, D., Borgström, B., Butler, G., Carel, J.-C., Cianfarani, S., Clayton, P., Coste, J., Deodati, A., Ecosse, E., Gausche, R., Giacomozzi, C., Hokken-Koelega, A. C. S., Khan, A. J., Kiess, W., Kuehni, C. E., Mullis, P.-E., Pfaffle, R., Sävendahl, L., Sommer, G., Thomas, M., Tidblad, A., Tollerfield, S., Van Eycken, L., & Zandwijken, G. R. J.
- Affiliations
- Institute of Cancer Research (GB)
- UCLouvain (BE)
- Karolinska Institutet (SE)
- National Health Service (GB)
- Inserm (FR)
- University of Rome Tor Vergata (IT)
- Leipzig University (DE)
- Azienda Ospedaliera Carlo Poma (IT)
- Erasmus MC (NL)
- University of Bern (CH)
- University Hospital of Bern (CH)
- University College London (GB)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-02-10
- Volume
- 102
- Issue
- 5
- Pages
- 1661-1672
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC6061931
- OpenAlex
- W2597357044
- Cited by
- 153
- References
- 31
- Citations by year
- 2026: 2 · 2025: 13 · 2024: 16 · 2023: 14 · 2022: 23 · 2021: 16 · 2020: 19 · 2019: 26 · 2018: 18 · 2017: 6
- FWCI
- 14.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion, cc-by)
- Digital Access to Libraries (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Open Access CRIS of the University of Bern
- Funders
- Eli Lilly and Company
- Pfizer
- University College London
- European Commission (223497)
- Cancerfonden
- Novo Nordisk
- Vetenskapsrådet
- Barncancerfonden
- Institut National Du Cancer
- Agence Française de Sécurité Sanitaire des Produits de Santé
- Ipsen
- Novo Nordisk Pharma
- FP7 Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Keywords
- recombinant human growth hormone, cancer risk, second primary malignancy, cancer mortality, cancer incidence, Hodgkin's disease, bone cancer, bladder cancer, growth hormone dose
- MeSH terms
- Adolescent, Urinary Bladder Neoplasms, Bone Diseases, Developmental, Bone Neoplasms, Child, Child, Preschool, Dose-Response Relationship, Drug, Europe, Female, Growth Disorders, Hodgkin Disease, Humans, Hypopituitarism, Infant, Infant, Newborn, Male, Neoplasms, Recombinant Proteins, Risk, Turner Syndrome, Cohort Studies, Incidence, Neoplasms, Second Primary, Human Growth Hormone, Renal Insufficiency, Chronic, Young Adult
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